Acetonitrile → tert-butyl 3(S)-[1(R)-ethoxycarbonyl-9-phthalimidononyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetate

HRID 280953Notes

Reaction equation

HRID 280953 reaction equation
[NH2:1][C@@H:2]1[C:8](=[O:9])[N:7]([CH2:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[C:6]2[CH:18]=[CH:19][CH:20]=[CH:21][C:5]=2[O:4][CH2:3]1.Br[CH:23]([CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][N:37]1[C:41](=[O:42])[C:40]2=[CH:43][CH:44]=[CH:45][CH:46]=[C:39]2[C:38]1=[O:47])[C:24]([O:26][CH2:27][CH3:28])=[O:25].C(#N)C>C(N(CC)CC)C>[CH2:27]([O:26][C:24]([C@H:23]([NH:1][C@@H:2]1[C:8](=[O:9])[N:7]([CH2:10][C:11]([O:13][C:14]([CH3:16])([CH3:17])[CH3:15])=[O:12])[C:6]2[CH:18]=[CH:19][CH:20]=[CH:21][C:5]=2[O:4][CH2:3]1)[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][N:37]1[C:38](=[O:47])[C:39]2=[CH:46][CH:45]=[CH:44][CH:43]=[C:40]2[C:41]1=[O:42])=[O:25])[CH3:28]

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 13622530tert-butyl 3(S)-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetateHCID 13622535Ethyl 2-bromo-10-phthalimidodecanoate

Product 1

HCID 13622569tert-butyl 3(S)-[1(R)-ethoxycarbonyl-9-phthalimidononyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetateYield 12.5%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of tert-butyl 3(S)-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetate (1.65 g), ethyl 2-bromo-10-phthalimidodecanoate (2.4 g), acetonitrile (100 ml) and triethylamine (0.75 g) is heated at 80° C. for 4 days. After evaporation of the solvent, ethyl acetate (200 ml) and water (100 ml) are added to the residue. The ethyl acetate layer is dried over anhydrous magnesium sulfate and evaporated in vacuo. The oily residue is chromatographed on silica gel using hexane-ethyl acetate (2:1) as an eluent. Evaporation of the first fraction gives tert-butyl 3(S)-[1(R)-ethoxycarbonyl-9-phthalimidononyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetate (0.45 g) as a colorless oil.

Workup

  1. customAfter evaporation of the solvent, ethyl acetate (200 ml) and water (100 ml)
  2. additionare added to the residue
  3. dry with materialThe ethyl acetate layer is dried over anhydrous magnesium sulfate
  4. customevaporated in vacuo
  5. customThe oily residue is chromatographed on silica gel
  6. customEvaporation of the first fraction

Sources & evidence

ORD record
ord-6c20d44a7d25491e911b90fe8bdef72b
Source dataset
uspto-grants-1986_05
Patent number
US04591458

Reaction notes

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